An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study)

Maximal benefits of coronary reperfusion after acute myocardial infarction (AMI) with ST-segment elevation may be attenuated by neutrophil-mediated re perfusion injury. Inflammatory mediators released from potentially viable m yocyles cause activation of neutrophils, which traverse the endothelium and enter the myocardium. This process involves interaction between the neutro phil-expressed CD11/CD18 and endothelial-expressed intercellular adhesion m olecule-1 (ICAM-1). Preclinical studies have shown that monoclonal antibodi es (MAb) to CD18 can limit infarct size and preserve left ventricular funct ion. We sought to determine the initial clinical safety and tolerability of Hu23F2G (LeukArrest), a humanized MAb to CD11/CD18, in patients with AMI w ho underwent percutaneous transluminal coronary angioplasty (PTCA). Sixty p atients with AMI were randomized to low- (0.3 mg/kg) or high-dose (1.0 mg/k g) Hu23F2G or to placebo immediately before PTCA. We found no clinically si gnificant differences in vital signs, physical examination, laboratory eval uation, or need for subsequent cardiac interventions. In Hu23F2G treatment groups, serum concentration of Hu23F2G increased rapidly to 3,234 +/- 1,298 mug/L (low-dose group) and 15,558 +/- 4409 mug/L (high-dose group) between 5 and 60 minutes, then declined over 72 hours to near-baseline values. Myo cardial single-photon emission computed tomographic imaging 120 to 260 hour s after PTCA showed no statistically significant differences in final left ventricular defect size. Hu23F2G was well tolerated, with no increase in ad verse events, including infections. Thus, Hu23F2G appears safe and well tol erated in patients undergoing PTCA for AMI. (C) 2001 by Excerpta Medica, In c.